Abstract P2-04-01: Immunoexpression of markers related to the HER2 pathway in cases of pure positive her2 breast carcinoma treated with trastuzumab
Authors: Andreia Fabiana V. Franco, Angela Flavia L. Waitzberg, Joaquim T. Araujo Neto, Fatima S. Pasini
Journal: Cancer Research (2023)

Abstract Introduction: Breast cancer is a heterogeneous disease with well-defined molecular subtypes and variable clinical behavior. The overexpressed HER2 subtype represents approximately 20% of all breast carcinomas. It is associated with a poor prognosis, increased risk of systemic and brain metastases, and poor overall survival until the advent of anti-HER2 therapies, such as trastuzumab. Its introduction into clinical practice has improved the prognosis in cases of breast cancer with overexpressing of pure HER2. However, some cases develop resistance to this drug. Objectives: To evaluate immunoexpression of possible markers involved in the HER2 pathway in breast carcinoma with overexpressing of pure HER2 treated with trastuzumab. Methods: We included 90 patients diagnosed with pure positive HER2 breast carcinoma treated with trastuzumab at the IBCC and HSP/Unifesp public hospitals between 2009 and 2018. Through immunohistochemistry, markers involved in the HER2 pathway (MUC4, IGF-1, IGF-1R, EGFR, p21, p27, p53, p16, cyclin D1, PTEN, CDK4, Bcl-2, VEGF, AR, MDM2, and TNFα) were analyzed samples paraffin-embedded of tumor and compromised lymph nodes and then, correlated with clinicopathological variables. The statistics were performed using the SPSS® software, version 25, from the company IBM, values equal to or less than 0.05 were considered significant (p ≤0.05). To verify possible associations between the clinical-pathological variables and the analyzed markers, Pearson’s X2 test, and Fisher’s exact test were used; for survival analysis, the Kaplan-Meier method was used. Results: Treatment resistance of pure HER2-positive breast cancer cases after trastuzumab treatment was 40%; the OS of this series was 4.13 years (95% CI 5.1 - 12.5) and the DFS was 3.6 years (95% CI 5.1 - 13.1). In the tumor samples it was possible to determine potential markers of good prognosis: cyclin D1 with nuclear grade (p=0.049) and recurrence (p=0.038); IGF-1 with tumor size (p= 0.015) and death (p= 0.046); p16 with response to treatment (p= 0.016); PTEN with response to treatment (p= 0.050) and death (p= 0.030). The results also showed possible markers of poor prognosis such as p53 with SBR GH (p= 0.003) and GN (p= 0.048); and IGF-1R with compromised lymph node (p=0.016). In compromised lymph nodes samples, the correlations showed TNFα with tumor size (p=0.043); and CDK4 with the response to treatment (p=0.011) as possible markers of good prognosis; only p53 with GH SBR grade (p= 0.045) maintained its potential for poor prognosis. Conclusions: In tumor samples, it was possible to demonstrate that the markers: cyclin D1, IGF-1, p16, and PTEN had the potential for a good prognosis panel and p53 and IGF-1R for worse. In samples of compromised lymph nodes, p53 remained as a marker of poor prognosis, while TNFα and CDK4 of good prognosis. Citation Format: Andreia Fabiana V. Franco, Angela Flavia L. Waitzberg, Joaquim T. Araujo Neto, Fatima S. Pasini. Immunoexpression of markers related to the HER2 pathway in cases of pure positive her2 breast carcinoma treated with trastuzumab [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-04-01.